Inhibition of Carcinogenesis by Tea and Tea Constituents

描述（由申请人提供）：这是一项新的R 01申请，用于研究茶多酚对癌症的化学预防作用的分子靶点。最近，我们已经确定了一些多酚（-）表没食子儿茶素3-没食子酸酯（EGCG）的结合蛋白。由于这些EGCG结合蛋白对细胞生长、肿瘤细胞转化和致瘤性至关重要，我们假设茶多酚EGCG及其衍生物的化学预防作用来自于它们对这些蛋白质的靶点。我们将利用3 H-EGCG细胞培养和蛋白质分析来检测茶多酚的抗肿瘤促进活性。本研究的具体目的是：1）研究新发现的EGCG结合蛋白在肿瘤促进剂诱导的细胞生长和细胞转化中的作用; 2）利用细胞培养模型研究EGCG结合蛋白在EGCG和其他茶多酚化学预防活性中的作用; 3）研究EGCG与其结合蛋白fyn和IGF-1 R的相互作用; 4）在肿瘤移植模型中研究fyn和IGF-1 R作为EGCG体内抗肿瘤作用的分子靶点的作用。我们已经建立了实验条件，通过初步调查，并期望拟议的分子机制研究将导致更好的化学预防剂的发展，并促进更有效的化学预防试验的设计。

DESCRIPTION (provided by applicant): This is a new R01 application to investigate the molecular targets of the chemopreventive effect on cancer by tea polyphenols. Recently, we have identified a few polyphenol (-)epigallocatechin 3-gallate (EGCG) binding proteins. Because these EGCG-binding proteins are critical for cell growth, neoplastic cell transformation and tumorigenicity, we hypothesize that the chemopreventive effect of the tea polyphenol EGCG and its derivatives is derived from their target on these proteins. We will use 3H-EGCG cell culture and protein analysis to examine the anti-tumor promotion activity of tea polyphenols. The specific aims to addrress the hypothesis are 1) to study the role of newly identified EGCG-binding proteins in tumor promoter-induced cell growth and cell transformation; 2) to study the role of EGCG-binding proteins in chemopreventive activity of EGCG and other tea polyphenols by using cell culture models; 3) to study the interactions of EGCG with its binding protein fyn and IGF-1R; 4) to study the role of fyn and IGF-1R as molecular targets for the anti-tumor effect of EGCG in vivo in tumor xenograft model. We have established experimental conditions through preliminary investigations and expect that the proposed molecular mechanism studies will lead to the development of better chemopreventive agents and facilitate the design of more effective chemoprevention trials.